Determinants of prognosis and management of patients with pulmonary hypertension due to left heart disease: a systematic review

Patients with pulmonary hypertension (PH) associated with left heart disease usually have a complex comorbidity status and a postcapillary component of PH. The presence and identification of a combined post-/precapillary PH in a cohort of patients with left heart disease is reflected in the more pronounced structural and functional right ventricular changes due to higher pulmonary vascular resistance. Patients with combined post-/ precapillary PH have reduced exercise tolerance and PH phenotype similar to pulmonary arterial hypertension. Detection of combined PH is critical as it may influence the prognosis and management of patients. This review presents modern prognosis markers for patients with PH due to left heart disease, which can be used in clinical practice. The results of randomized clinical trials and pilot studies on the expansion of treatment options in group 2 patients, including the use of PAH-specific agents, were analyzed. The prospects for the treatment of this cohort of patients are discussed

First Results of the Phase II SIMPLE Dark Matter Search

We report results of a 14.1 kgd measurement with 15 superheated droplet detectors of total active mass 0.208 kg, comprising the first stage of a 30 kgd Phase II experiment. In combination with the results of the neutron-spin sensitive XENON10 experiment, these results yield a limit of |a_p| < 0.32 for M_W = 50 GeV/c2 on the spin-dependent sector of weakly interacting massive particle-nucleus interactions with a 50% reduction in the previously allowed region of the phase space formerly defined by XENON, KIMS and PICASSO. In the spin-independent sector, a limit of 2.3x10-5 pb at M_W = 45 GeV/c2 is obtained.Comment: 4 pages, 4 figures; PRL-accepted version with corrected SI contour (Fig. 4

Фенотип пациентов с легочной гипертензией вследствие патологии левых отделов сердца: особенности патофизиологии и дифференциальной диагностики

The cohort of patients with postcapillary pulmonary hypertension (PH), associated with the left heart diseases, is the most numerous, but is still not fully understood. This review presents the pathophysiological aspects of the PH group 2 development as well as the influence of comorbid pathology on the course of the PH. The features of the differential diagnosis of post-capillary PH and combined post-/ precapillary PH, as well as methods of the differential diagnosis of these forms of PH with pulmonary arterial hypertension using modern non-invasive and invasive approaches are discussed.Наиболее многочисленной, при этом не до конца изученной остается когорта пациентов с посткапиллярной легочной гипертензией (ЛГ), ассоциированной с заболеваниями левых отделов сердца. В данном обзоре детально представлены патофизиологические аспекты развития ЛГ на фоне патологии левых отделов сердца на примере сердечной недостаточности с низкой/сохранной фракцией выброса, а также описано влияние коморбидной патологии на характер течения ЛГ. Обсуждены особенности дифференциального диагноза посткапиллярной и комбинированной (пост- и прекапиллярной) форм ЛГ, а также подходы к дифференциальному диагнозу данных форм ЛГ с легочной артериальной гипертензией с использованием современных неинвазивных и инвазивных подходов.

Prospects for SIMPLE 2000: A large-mass, low-background Superheated Droplet Detector for WIMP searches

SIMPLE 2000 (Superheated Instrument for Massive ParticLE searches) will consist of an array of eight to sixteen large active mass ($\sim15$ g) Superheated Droplet Detectors(SDDs) to be installed in the new underground laboratory of Rustrel-Pays d'Apt. Several factors make of SDDs an attractive approach for the detection of Weakly Interacting Massive Particles (WIMPs), namely their intrinsic insensitivity to minimum ionizing particles, high fluorine content, low cost and operation near ambient pressure and temperature. We comment here on the fabrication, calibration and already-competitive first limits from SIMPLE prototype SDDs, as well as on the expected immediate increase in sensitivity of the program, which aims at an exposure of $>$25 kg-day during the year 2000. The ability of modest-mass fluorine-rich detectors to explore regions of neutralino parameter space beyond the reach of the most ambitious cryogenic projects is pointed out.Comment: 19 pages, 10 figures included. New Journal of Physics, in pres

First Dark Matter Limits from a Large-Mass, Low-Background Superheated Droplet Detector

We report on the fabrication aspects and calibration of the first large active mass ($\sim15$ g) modules of SIMPLE, a search for particle dark matter using Superheated Droplet Detectors (SDDs). While still limited by the statistical uncertainty of the small data sample on hand, the first weeks of operation in the new underground laboratory of Rustrel-Pays d'Apt already provide a sensitivity to axially-coupled Weakly Interacting Massive Particles (WIMPs) competitive with leading experiments, confirming SDDs as a convenient, low-cost alternative for WIMP detection.Comment: Final version, Phys. Rev. Lett. (in press

The influence of antyhypertensive therapy of valsartan and fixed combination with hydrochlorothiazide use on pulse-wave velocity and central arterial pressure in patients with arterial hypertension of 1-2 grades in international VICTORY clinical trial

Objective - to explore influence of valsartan monotherapy use and its use in combination with hydrochlorothiazide (HCTZ) on pulse-wave velocity (PWV) and central arterial pressure (CAP) in patients with arterial hypertension (AH) of 1-2 grades in international VICTORY clinical trial. Materials and methods. The international multicenter prospective randomized clinical study VICTORY that lasted for 16 weeks included patients with 1-2 grades AH. In patients who previously received antihypertensive therapy a 7 days washout period was carried out. All patients started their therapy with 80 mg valsartan (Valsacor®, KRKA, Slovenia); in Russia the starter dose of Valsacor®, KRKA was 160 mg in previously treated patients that did not influence the study results. If after 4 weeks of treatment BP was more than 140/90 mm hg (more than 130/80 mm hg in high risk patients or in diabetes mellitus patients) the dose of valsartan was increased to 160 mg (320 mg in Russia) or diuretic in fixed combination with valsartan was added (160 mg valsartan/12.5 mg HCTZ): Valsacor® H 160 (KRKA, Slovenia). If target BP after 8 weeks of treatment was not reached valsartan dose was increased to 320 mg or fixed combination of valsartan and diuretic (160 mg/12.5 mg) was used. If target BP after 12 weeks of treatment was not reached - valsartan and diuretic 320 mg/12.5 mg were used. PWV and CAP (SphygmoCor®, AtCorMedical) were assessed at baseline and after 16 weeks of treatment. The primary endpoints were assessment of the impact of studied medications on aortic stiffness, aortic augmentation index and comparison of absolute medians of reached central and peripheral BP reduction with baseline value. Results. Of 365 patients included in the study 74 were included in PWV and CAP study subgroup. Valsartan and its combination with HCTZ were effective in CBP reduction. The mean absolute reduction of central systolic and diastolic BP after 16 weeks of treatment was 19.7±12.9 mm hg and 13.9±8.5 mm hg, respectively (

СУБТРАКЦИОННАЯ КТ-АНГИОПУЛЬМОНОГРАФИЯ В ДИАГНОСТИКЕ ХРОНИЧЕСКОЙ ТРОМБОЭМБОЛИЧЕСКОЙ ЛЕГОЧНОЙ ГИПЕРТЕНЗИИ

Purpose. To assess the state of the vascular bed and perfusion of the lungs in patients with chronic thromboembolic pulmonary hypertension (CTEPH) by the method of subtraction computed tomography (CT).Materials and methods. Between November 2015 and May 2018, 65 patients with diagnosis of CTEPH were examined. All patients were examined on a computer tomograph Aquilion ONE 640 VISION Edition (Toshiba Medical Systems) with 320 rows of detectors, slice thickness – 0,5 mm. Assessment of perfusion disorders was carried out using new software, which allows combining contrast and noncontrast images by subtraction. Were analyzed parameters of the parenchyma, blood supply and perfusion status with the calculation of indices of obstruction and perfusion disorders. The obstruction index was compared with the index of perfusion abnormalities, a 6-minute walk test, and mean pulmonary artery pressure according to the right heart catheterization data. Results. The significant correlation was found between the obstruction index and the index of perfusion disorders in patients with CTEPH (r = 0.605; p = 0.000001). Interrelations between vascular-perfusion indices (an obstruction index and an index of perfusion disorders), mean pulmonary artery pressure and distance in a 6-minute walk test were not revealed.Conclusion. Subtraction CT pulmonary angiography allows to assess the severity of vascular lesion and perfusion disorders within a single study, also determine the effectiveness of treatment in patients with CTEPH.Цель исследования: оценить состояние сосудистого русла и перфузии легких у больных хронической тромбоэмболической легочной гипертензией (ХТЭЛГ) методом субтракционной компьютерной томографии (КТ).Материал и методы. В период с ноября 2015 г. по май 2018 г. было обследовано 65 пациентов с диагнозом ХТЭЛГ. Все пациенты были обследованы на компьютер-ном томографе Aquilion ONE 640 VISION Edition (Toshiba Medical Systems) с 320 рядами детекторов, толщина томографического среза 0,5 мм. Оценка перфузионных нарушений выполнялась с помощью нового программного обеспечения, которое позволяет совмещать контрастные и бесконтрастные изображения методом субтракции. Анализировались параметры состояния паренхимы, кровоснабжения и перфузии легких с расчетом индексов обструкции и перфузионных нарушений. Индекс обструкции был сопоставлен с индексом перфузионных нарушений, тестом 6-минутной ходьбы (Т6МХ) и средним давлением в легочной артерии (ср. ДЛА) по данным катетеризации правых отделов сердца.Результаты. Между индексом обструкции и индексом перфузионных нарушений у больных ХТЭЛГ была обнаружена статистически значимая корреляция (r = 0,605; p = 0,000001). Взаимосвязей между сосудисто-перфузионными показателями (индексом обструкции и индексом перфузионных нарушений), ср.ДЛА и пройденной дистанцией в Т6МХ выявлено не было.Заключение. Использование субтракционной КТ-ангиопульмонографии позволяет оценить выраженность сосудистого поражения и перфузионных нарушений в рамках одного исследования, а также определить эффективность лечения у пациентов с ХТЭЛГ

Проблемні питання визначення правової природи і структури правовідносин інтелектуальної власності, що виникають у мережі Інтернет

Харитонова О. І., Ульянова Г. О., Кирилюк А. В., Симонян Ю. Ю., Бааджи Н. П., Позова Д. Д., Григор'янц Г. І., Бурова Л. І., Мартинюк І. В. Проблемні питання визначення правової природи і структури правовідносин інтелектуальної власності, що виникають у мережі Інтернет / О. І. Харитонова, Г. О.Ульянова, А. В. Кирилюк, Ю. Ю. Симонян, Н. П. Бааджи, Д. Д. Позова, Г. І. Григор'янц, Л. І. Бурова, І. В. Мартинюк // Наукові праці Національного університету «Одеська юридична академія». Т. 17 / голов. ред. М. В. Афанасьєва ; МОН України, НУ «ОЮА». – Одеса : Юрид. л-ра, 2015. – C. 159-200.Сьогодні під впливом науково-технічного прогресу значно розширилось коло суспільних відносин. Виникає така категорія правовідносин, як «правовідносини в мережі Інтернет». Постає питання правового регулювання таких відносин, суб'єктного складу, змісту та з приводу чого вони виникають. Саме ці питання розкриті в даній статті

Effect of SGLT2 inhibitors on stroke and atrial fibrillation in diabetic kidney disease: Results from the CREDENCE trial and meta-analysis

BACKGROUND AND PURPOSE: Chronic kidney disease with reduced estimated glomerular filtration rate or elevated albuminuria increases risk for ischemic and hemorrhagic stroke. This study assessed the effects of sodium glucose cotransporter 2 inhibitors (SGLT2i) on stroke and atrial fibrillation/flutter (AF/AFL) from CREDENCE (Canagliflozin and Renal Events in Diabetes With Established Nephropathy Clinical Evaluation) and a meta-Analysis of large cardiovascular outcome trials (CVOTs) of SGLT2i in type 2 diabetes mellitus. METHODS: CREDENCE randomized 4401 participants with type 2 diabetes mellitus and chronic kidney disease to canagliflozin or placebo. Post hoc, we estimated effects on fatal or nonfatal stroke, stroke subtypes, and intermediate markers of stroke risk including AF/AFL. Stroke and AF/AFL data from 3 other completed large CVOTs and CREDENCE were pooled using random-effects meta-Analysis. RESULTS: In CREDENCE, 142 participants experienced a stroke during follow-up (10.9/1000 patient-years with canagliflozin, 14.2/1000 patient-years with placebo; hazard ratio [HR], 0.77 [95% CI, 0.55-1.08]). Effects by stroke subtypes were: ischemic (HR, 0.88 [95% CI, 0.61-1.28]; n=111), hemorrhagic (HR, 0.50 [95% CI, 0.19-1.32]; n=18), and undetermined (HR, 0.54 [95% CI, 0.20-1.46]; n=17). There was no clear effect on AF/AFL (HR, 0.76 [95% CI, 0.53-1.10]; n=115). The overall effects in the 4 CVOTs combined were: Total stroke (HRpooled, 0.96 [95% CI, 0.82-1.12]), ischemic stroke (HRpooled, 1.01 [95% CI, 0.89-1.14]), hemorrhagic stroke (HRpooled, 0.50 [95% CI, 0.30-0.83]), undetermined stroke (HRpooled, 0.86 [95% CI, 0.49-1.51]), and AF/AFL (HRpooled, 0.81 [95% CI, 0.71-0.93]). There was evidence that SGLT2i effects on total stroke varied by baseline estimated glomerular filtration rate (P=0.01), with protection in the lowest estimated glomerular filtration rate (45 mL/min/1.73 m2]) subgroup (HRpooled, 0.50 [95% CI, 0.31-0.79]). CONCLUSIONS: Although we found no clear effect of SGLT2i on total stroke in CREDENCE or across trials combined, there was some evidence of benefit in preventing hemorrhagic stroke and AF/AFL, as well as total stroke for those with lowest estimated glomerular filtration rate. Future research should focus on confirming these data and exploring potential mechanisms

Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to 300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute per 1.73 m 2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P<0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years